A sequential and synergistic release sacrificial microgels scaffold for endometrial niche reprogramming and fertility restoration.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Intrauterine adhesions (IUA) remain a therapeutic challenge, necessitating advanced regenerative strategies. Herein, we propose a "programmed endometrial niche" strategy, a 3D-printed adipose-derived stem cells (ADSCs) hydrogel scaffold is constructed via microfluidic technology, incorporating platelet-rich plasma (PRP)-loaded thermosensitive gelatin microgels (PMS@AH) for sequential and synergistic delivery of PRP and ADSCs to restore the endometrial immune microenvironment and niche. In vitro assays demonstrate that PMS@AH possesses excellent biocompatibility and significantly promoted cell proliferation, migration, and angiogenesis, accompanied by potent anti-inflammatory activity. In both rat and cynomolgus macaque IUA models, it effectively restored endometrial structure, reduced fibrosis and inflammation, and successfully restored fertility. Mechanistically, RNA-sequencing analysis reveals that PMS@AH involves suppressing the IL-17/nuclear factor-κB (NF-κB) pathway to modulate the immune microenvironment and inhibiting the Wnt/β-catenin pathway to program the endometrial niche. This sequentially releasing scaffold presents a promising platform for treating IUA and broader applications in reproductive medicine.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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